Skip to main content
padlock icon - secure page this page is secure

WF-536 INHIBITS METASTATIC INVASION BY ENHANCING THE HOST CELL BARRIER and INHIBITING TUMOUR CELL MOTILITY

Buy Article:

$52.00 + tax (Refund Policy)

Summary

1. Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK) is involved in the development of tumour metastasis. Wf-536, (+)-(R)-4-(1-Aminoethyl)-N-(4-pyridyl) benzamide monohydrochloride, a novel inhibitor of ROCK, inhibits tumour metastasis in some animal models. To metastasise, tumour cells have to disturb the tight intercellular junctions and the basement membrane matrix of the host tissue, which, respectively, create an intercellular barrier and the extracellular membrane. To clarify the mechanism of Wf-536 in inhibition of tumour metastasis, we analysed the effect of Wf-536 on the transition of tumour cells through the host cell layer and the basement membrane in in vitro systems.

2. In a coculture system of human fibrosarcoma HT1080 cells plated on a monolayer of human ECV304 cells, Wf-536 (0.3–3 µmol/L) inhibited the paracellular infiltration of tumour cells.

3. Wf-536 (3–30 µmol/L) inhibited the invasion of tumour cells through the reconstituted basement membrane (Matrigel) layer.

4. Wf-536 (10–30 µmol/L) inhibited the migration of tumour cells. At 0.3–3 µmol/L, Wf-536 also restrained hepatocyte growth factor/scatter factor (HGF)-induced increases in paracellular permeability of the ECV304 cell layer.

5. These results suggest that Wf-536 suppresses tumour metastasis by both enhancing the barrier function of host cell layers and inhibiting tumour cell motility at the stage of host tissue penetration by metastatic tumour cells.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Keywords: Rho-associated coiled-coil forming protein serine; Wf-536; motility; paracellular infiltration; paracellular permeability; rho; threonine kinase; tumor cells

Document Type: Research Article

Affiliations: Pharmaceuticals Research Unit, Mitsubishi Pharma Corporation, Kanagawa, Japan

Publication date: July 1, 2003

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more